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Oxidative Stress, Hypoxia and Cellular Metabolism: Unraveling the Effects of Fentanyl on Lung Cancer Cells

Sharma, A.; Das, R. K.; Kuzmin, A.; Shukla, S.; Prasad, P. N.; Mahajan, S. D.

2025-07-22 cancer biology
10.1101/2025.07.17.665412 bioRxiv
Show abstract

Fentanyl, a widely used opioid analgesic for cancer pain management, is effective but requires cautious administration due to its potential for respiratory depression. Beyond its analgesic properties, fentanyls broader impact on cancer biology and biochemical alterations in lung carcinoma cells remains underexplored. This study investigates fentanyls influence on oxidative stress, mitochondrial function, hypoxia-inducing factors, apoptosis, and cytokine production in A549 lung cancer cells. Our findings reveal that fentanyl increases reactive oxygen species (ROS) generation, disrupts cellular homeostasis, induces DNA damage, and alters key signaling pathways, potentially affecting tumor metabolism and progression. Our "Ramanomics" data further highlight fentanyl-driven changes in key ions (inorganic phosphate, calcium) and biomolecules (glycogen, phospholipids, proteins, nucleic acids, and enzymes) at subcellular mitochondrial levels. These insights contribute to understanding fentanyls mechanistic impact on lung cancer progression and may inform optimized therapeutic strategies. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/665412v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@1fb7aaaorg.highwire.dtl.DTLVardef@13255deorg.highwire.dtl.DTLVardef@1a398cdorg.highwire.dtl.DTLVardef@184d63e_HPS_FORMAT_FIGEXP M_FIG C_FIG

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